ABSTRACT The principal Phase II goal of the COBRE Center for Targeted Therapeutics (CTT) is to conduct vital research oriented at identifying novel drug targets and discovering new targeted drugs, while enhancing the career development and research competitiveness of Center investigators. Targeted therapeutics is a broad term for research that seeks to develop new and more effective classes of drugs against various diseases, by selectively aiming these drugs at molecular and cellular targets that play a key role in the disease. The area of Targeted Therapeutics has been chosen because of its societal impact, the emergence of common technologies driving therapeutics research in different disease areas, and the presence of a critical core of senior faculty with broad acumen and trans-disciplinary vision in Targeted Therapeutics at USC. During Phase I, junior investigators leading CTT research projects (target PIs) were awarded five R01s and several smaller grants, and pilot project recipients received two R01s and several other grants, for a total of close to $14 million. Four target PIs received promotion and tenure and almost 50 published papers acknowledged COBRE support. Three resource cores established by the CTT provided services to 64 different laboratories and organized training workshops and a new graduate course. To build upon the success of Phase I, we will pursue the following Specific Aims. Aim 1. Support high-impact research projects and assist junior scientists in Targeted Therapeutics in their professional development and competitiveness for NIH grants, in a collaborative and nurturing environment. Target junior faculty members include four highly promising scientists, each of whom will be mentored by two senior scientists with different areas of expertise relevant to their research. Aim 2. Establish sustainable research infrastructure through the further development of strategic Cores for Targeted Therapeutics research. The Center supports research cores in Functional Genomics, Drug Design and Synthesis, and Microscopy and Flow Cytometry. These cores will provide both specialized services and intellectual scientific support. Aim 3. Assure long-term development of the CTT by broadening collaborative networking, fostering continuous recruitment, supporting new faculty in Targeted Therapeutics, and supporting pilot research projects, with an emphasis on drug discovery and preparation for multi-investigator and SBIR/STTR grant applications. CTT will conduct regular meetings and seminars and promote external collaborations. CTT will participate in the recruitment of five new junior faculty members to USC and will continue working with the ?graduated? target faculty, assuring that they continue to make important discoveries and win grants. Continued success of the CTT will make an impact on the public health, scientific education and economic development of the State.